trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(2-pyridyloxy)-2H-1-benzopyran

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(2-pyridyloxy)-2H-1-benzopyran
• 化学式: C₁₆H₁₇NO₃
• 分子量: 271.316
• InChiKey: YLQRPGSVELIKIA-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.73
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  51.58
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  2,2,-二甲基-2H-苯并吡喃 在 吡啶 、 氢氧化钾 、 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙醚 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 48.5h， 生成 trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(2-pyridyloxy)-2H-1-benzopyran
  参考文献：
  名称：

  6-Substituted Benzopyrans as Potassium Channel Activators:  Synthesis, Vasodilator Properties, and Multivariate Analysis

  摘要：

  During the last 10 years compounds have been discovered which can activate or block K-ATP channels. In particular, K channel activators (KCA)have been found to be smooth muscle relaxants with their main utility in hypertension and bronchodilation. In this paper we describe the synthesis of new KCA of the benzopyran type with a fixed 4-substituent and a systematic variation in the 6-position. The relaxant potency in rat aorta and trachea was used for biological characterization of the benzopyrans. In both biological test systems, they exhibit potency ranges of more than 3 log units. Structure-activity relationships are investigated by principal component analysis (PCA) and partial least-squares (PLS) analysis. Most striking outliers in an initial PLS analysis of the entire database were the unsubstituted 6-H compound 13 as well as 34 and 35. For the remaining set of 31 compounds, a S-component PLS model explains the variance in biological activity to 81% in the aortic and to 82% in the tracheal test system. 6-Substituents influence affinity by a direct (presumably dipolar) interaction with the receptor site. According to the 2D-plot of the partial PLS weights, a strong electronegativity as well as high values for the integy moment and for the heat of formation in water dominate the first component; low values for substituent size (as defined by globularity or surface) are in addition favorable for high potency. High lipophilicity and low minimum energies of interaction dominate the second component. Chemical descriptors for the biological potency of the test set in rat aorta and rat trachea are very similar according to the almost identical projection of the Y-variables onto the X-component space.

  DOI：

  10.1021/jm981047m

文献信息

• 6-Substituted Benzopyrans as Potassium Channel Activators:  Synthesis, Vasodilator Properties, and Multivariate Analysis
  作者：Raimund Mannhold、Gabriele Cruciani、Horst Weber、Horst Lemoine、Andrea Derix、Claus Weichel、Monica Clementi

  DOI：10.1021/jm981047m

  日期：1999.3.1

  During the last 10 years compounds have been discovered which can activate or block K-ATP channels. In particular, K channel activators (KCA)have been found to be smooth muscle relaxants with their main utility in hypertension and bronchodilation. In this paper we describe the synthesis of new KCA of the benzopyran type with a fixed 4-substituent and a systematic variation in the 6-position. The relaxant potency in rat aorta and trachea was used for biological characterization of the benzopyrans. In both biological test systems, they exhibit potency ranges of more than 3 log units. Structure-activity relationships are investigated by principal component analysis (PCA) and partial least-squares (PLS) analysis. Most striking outliers in an initial PLS analysis of the entire database were the unsubstituted 6-H compound 13 as well as 34 and 35. For the remaining set of 31 compounds, a S-component PLS model explains the variance in biological activity to 81% in the aortic and to 82% in the tracheal test system. 6-Substituents influence affinity by a direct (presumably dipolar) interaction with the receptor site. According to the 2D-plot of the partial PLS weights, a strong electronegativity as well as high values for the integy moment and for the heat of formation in water dominate the first component; low values for substituent size (as defined by globularity or surface) are in addition favorable for high potency. High lipophilicity and low minimum energies of interaction dominate the second component. Chemical descriptors for the biological potency of the test set in rat aorta and rat trachea are very similar according to the almost identical projection of the Y-variables onto the X-component space.